Trial Outcomes & Findings for Clinical Trial of Glatiramer Acetate in Amyotrophic Lateral Sclerosis (ALS) (NCT NCT00326625)

Last Updated: 2022-08-03

Results Overview

The ALSFRS-R is a questionnaire-based scale for monitoring the progression of disability in patients with ALS. It is composed of 12 items, each scored between 0 and 4.The total score, calculated as the sum of these 12 items, ranges from 0 to 48. The higher the score, the less disabled the participant. Timepoints after baseline were included in calculation of slope of change in ALSFRS-R. Slope is derived from the time by treatment interaction term from the Repeated Measures Analysis of Covariance model. Descriptive statistics of the slope are reported.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

366 participants

Primary outcome timeframe

Baseline, Weeks 4, 8, 12, 17, 22, 26, 31, 36, 40, 44, 48, 52

Results posted on

2022-08-03

Participant Flow

366 participants were randomized in a 1:1 ratio to one of two treatment groups, Glatiramer Acetate 40 mg or matching placebo. The study duration was 52 weeks with a follow up period of up to 44 weeks.

Participant milestones

Participant milestones
Measure	Glatiramer Acetate 40mg Pre-filled syringe of 40 mg glatiramer acetate (GA) for injection, administered subcutaneously once a day	Placebo Pre-filled syringe of matching placebo, administered subcutaneously once a day
Overall Study STARTED	184	182
Overall Study COMPLETED	130	144
Overall Study NOT COMPLETED	54	38

Reasons for withdrawal

Reasons for withdrawal
Measure	Glatiramer Acetate 40mg Pre-filled syringe of 40 mg glatiramer acetate (GA) for injection, administered subcutaneously once a day	Placebo Pre-filled syringe of matching placebo, administered subcutaneously once a day
Overall Study Adverse Event	20	9
Overall Study Withdrawal by Subject	15	12
Overall Study Death	18	16
Overall Study Lost to Follow-up	1	0
Overall Study prescheduled medical intervention	0	1

Baseline Characteristics

Clinical Trial of Glatiramer Acetate in Amyotrophic Lateral Sclerosis (ALS)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Glatiramer Acetate 40mg n=184 Participants Pre-filled syringe of 40 mg glatiramer acetate (GA) for injection, administered subcutaneously once a day	Placebo n=182 Participants Pre-filled syringe of matching placebo, administered subcutaneously once a day	Total n=366 Participants Total of all reporting groups
Age, Continuous	55.7 Years STANDARD_DEVIATION 9.6 • n=5 Participants	54.7 Years STANDARD_DEVIATION 9.6 • n=7 Participants	55.2 Years STANDARD_DEVIATION 9.6 • n=5 Participants
Sex: Female, Male Female	69 Participants n=5 Participants	72 Participants n=7 Participants	141 Participants n=5 Participants
Sex: Female, Male Male	115 Participants n=5 Participants	110 Participants n=7 Participants	225 Participants n=5 Participants
Race/Ethnicity, Customized White	182 Participants n=5 Participants	182 Participants n=7 Participants	364 Participants n=5 Participants
Race/Ethnicity, Customized Black or African American	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race/Ethnicity, Customized Hispanic	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline, Weeks 4, 8, 12, 17, 22, 26, 31, 36, 40, 44, 48, 52

Population: The intent-to-treat (ITT) analysis set consisted of all randomized participants who took at least one dose of the study drug.

Outcome measures

Outcome measures
Measure	Glatiramer Acetate 40mg n=184 Participants Pre-filled syringe of 40 mg glatiramer acetate (GA) for injection, administered subcutaneously once a day	Placebo n=182 Participants Pre-filled syringe of matching placebo, administered subcutaneously once a day
Slope of Change From Baseline in the ALS Functional Rating Scale (ALSFRS-R)	-1.05 Units on a Scale per Month Standard Error 0.059	-1.00 Units on a Scale per Month Standard Error 0.058

SECONDARY outcome

Timeframe: Baseline up to 52 weeks

Population: The intent-to-treat (ITT) analysis set consisted of all randomized participants who took at least one dose of the study drug.

Composite endpoint of time to death, tracheostomy, or permanent assisted ventilation analyzed using the Cox's proportional hazards model to compare the risk of death, tracheostomy, or permanent assisted ventilation between treatment groups. The model includes center country, Riluzole© use, site of ALS onset, time from ALS onset, and baseline ALSFRS-R score, baseline slow VC and baseline BMI as covariates. Because less than 50% of participants experienced the event, the median time to event (i.e. the descriptive statistic for the day for which 50% of participants experienced the event) could not be calculated. Hence the days are reported as not available.

Outcome measures

Outcome measures
Measure	Glatiramer Acetate 40mg n=184 Participants Pre-filled syringe of 40 mg glatiramer acetate (GA) for injection, administered subcutaneously once a day	Placebo n=182 Participants Pre-filled syringe of matching placebo, administered subcutaneously once a day
Time to Event: Death, Tracheostomy, Permanent Assisted Ventilation	NA Days Median days to event could not be calculated because less than 50% of participants experienced the event. Hence the days are reported as NA.	NA Days Median days to event could not be calculated because less than 50% of participants experienced the event. Hence the days are reported as NA.

Adverse Events

Glatiramer Acetate 40mg

Serious events: 55 serious events

Other events: 167 other events

Deaths: 22 deaths

Placebo

Serious events: 54 serious events

Other events: 133 other events

Deaths: 17 deaths

Serious adverse events

Other adverse events

Additional Information

Director, Clinical Research

Teva Branded Pharmaceutical Products, R&D Inc.

Phone: 1-888-483-8279

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Sponsor has the right 60 days before submission for publication to review/provide comments. If the Sponsor's review shows that potentially patentable subject matter would be disclosed, publication or public disclosure shall be delayed for up to 90 additional days in order for the Sponsor, or Sponsor's designees, to file the necessary patent applications. In multicenter trials, each PI will postpone single center publications until after disclosure or publication of multicenter data.
Publication restrictions are in place

Restriction type: OTHER

Measure	Glatiramer Acetate 40mg n=184 participants at risk Pre-filled syringe of 40 mg glatiramer acetate (GA) for injection, administered subcutaneously once a day	Placebo n=182 participants at risk Pre-filled syringe of matching placebo, administered subcutaneously once a day
Gastrointestinal disorders Constipation	9.8% 18/184 • Number of events 18 • Baseline up to 96 weeks. The safety analysis set included all participants that took at least one dose of study drug.	7.7% 14/182 • Number of events 15 • Baseline up to 96 weeks. The safety analysis set included all participants that took at least one dose of study drug.
Gastrointestinal disorders Diarrhoea	9.2% 17/184 • Number of events 23 • Baseline up to 96 weeks. The safety analysis set included all participants that took at least one dose of study drug.	7.1% 13/182 • Number of events 18 • Baseline up to 96 weeks. The safety analysis set included all participants that took at least one dose of study drug.
Gastrointestinal disorders Dysphagia	6.0% 11/184 • Number of events 12 • Baseline up to 96 weeks. The safety analysis set included all participants that took at least one dose of study drug.	4.9% 9/182 • Number of events 10 • Baseline up to 96 weeks. The safety analysis set included all participants that took at least one dose of study drug.
Gastrointestinal disorders Nausea	9.2% 17/184 • Number of events 20 • Baseline up to 96 weeks. The safety analysis set included all participants that took at least one dose of study drug.	6.0% 11/182 • Number of events 12 • Baseline up to 96 weeks. The safety analysis set included all participants that took at least one dose of study drug.
General disorders Fatigue	6.0% 11/184 • Number of events 11 • Baseline up to 96 weeks. The safety analysis set included all participants that took at least one dose of study drug.	7.7% 14/182 • Number of events 15 • Baseline up to 96 weeks. The safety analysis set included all participants that took at least one dose of study drug.
General disorders Injection site erythema	43.5% 80/184 • Number of events 239 • Baseline up to 96 weeks. The safety analysis set included all participants that took at least one dose of study drug.	4.9% 9/182 • Number of events 11 • Baseline up to 96 weeks. The safety analysis set included all participants that took at least one dose of study drug.
General disorders Injection site induration	13.0% 24/184 • Number of events 24 • Baseline up to 96 weeks. The safety analysis set included all participants that took at least one dose of study drug.	0.55% 1/182 • Number of events 1 • Baseline up to 96 weeks. The safety analysis set included all participants that took at least one dose of study drug.
General disorders Injection site mass	8.2% 15/184 • Number of events 16 • Baseline up to 96 weeks. The safety analysis set included all participants that took at least one dose of study drug.	0.00% 0/182 • Baseline up to 96 weeks. The safety analysis set included all participants that took at least one dose of study drug.
General disorders Injection site nodule	6.0% 11/184 • Number of events 58 • Baseline up to 96 weeks. The safety analysis set included all participants that took at least one dose of study drug.	0.55% 1/182 • Number of events 1 • Baseline up to 96 weeks. The safety analysis set included all participants that took at least one dose of study drug.
General disorders Injection site pain	28.3% 52/184 • Number of events 81 • Baseline up to 96 weeks. The safety analysis set included all participants that took at least one dose of study drug.	4.4% 8/182 • Number of events 8 • Baseline up to 96 weeks. The safety analysis set included all participants that took at least one dose of study drug.
General disorders Injection site pruritus	25.0% 46/184 • Number of events 181 • Baseline up to 96 weeks. The safety analysis set included all participants that took at least one dose of study drug.	1.6% 3/182 • Number of events 3 • Baseline up to 96 weeks. The safety analysis set included all participants that took at least one dose of study drug.
General disorders Injection site swelling	13.0% 24/184 • Number of events 72 • Baseline up to 96 weeks. The safety analysis set included all participants that took at least one dose of study drug.	0.00% 0/182 • Baseline up to 96 weeks. The safety analysis set included all participants that took at least one dose of study drug.
General disorders Malaise	5.4% 10/184 • Number of events 16 • Baseline up to 96 weeks. The safety analysis set included all participants that took at least one dose of study drug.	2.7% 5/182 • Number of events 8 • Baseline up to 96 weeks. The safety analysis set included all participants that took at least one dose of study drug.
General disorders Oedema peripheral	2.7% 5/184 • Number of events 5 • Baseline up to 96 weeks. The safety analysis set included all participants that took at least one dose of study drug.	5.5% 10/182 • Number of events 11 • Baseline up to 96 weeks. The safety analysis set included all participants that took at least one dose of study drug.
Infections and infestations Bronchitis	6.5% 12/184 • Number of events 14 • Baseline up to 96 weeks. The safety analysis set included all participants that took at least one dose of study drug.	10.4% 19/182 • Number of events 20 • Baseline up to 96 weeks. The safety analysis set included all participants that took at least one dose of study drug.
Infections and infestations Nasopharyngitis	16.8% 31/184 • Number of events 38 • Baseline up to 96 weeks. The safety analysis set included all participants that took at least one dose of study drug.	16.5% 30/182 • Number of events 40 • Baseline up to 96 weeks. The safety analysis set included all participants that took at least one dose of study drug.
Infections and infestations Upper respiratory tract infection	5.4% 10/184 • Number of events 12 • Baseline up to 96 weeks. The safety analysis set included all participants that took at least one dose of study drug.	4.9% 9/182 • Number of events 12 • Baseline up to 96 weeks. The safety analysis set included all participants that took at least one dose of study drug.
Infections and infestations Urinary tract infection	4.3% 8/184 • Number of events 10 • Baseline up to 96 weeks. The safety analysis set included all participants that took at least one dose of study drug.	5.5% 10/182 • Number of events 14 • Baseline up to 96 weeks. The safety analysis set included all participants that took at least one dose of study drug.
Injury, poisoning and procedural complications Fall	20.1% 37/184 • Number of events 65 • Baseline up to 96 weeks. The safety analysis set included all participants that took at least one dose of study drug.	24.7% 45/182 • Number of events 105 • Baseline up to 96 weeks. The safety analysis set included all participants that took at least one dose of study drug.
Musculoskeletal and connective tissue disorders Back pain	9.8% 18/184 • Number of events 20 • Baseline up to 96 weeks. The safety analysis set included all participants that took at least one dose of study drug.	8.2% 15/182 • Number of events 15 • Baseline up to 96 weeks. The safety analysis set included all participants that took at least one dose of study drug.
Musculoskeletal and connective tissue disorders Muscle spasms	5.4% 10/184 • Number of events 12 • Baseline up to 96 weeks. The safety analysis set included all participants that took at least one dose of study drug.	1.6% 3/182 • Number of events 3 • Baseline up to 96 weeks. The safety analysis set included all participants that took at least one dose of study drug.
Musculoskeletal and connective tissue disorders Muscular weakness	6.0% 11/184 • Number of events 18 • Baseline up to 96 weeks. The safety analysis set included all participants that took at least one dose of study drug.	9.9% 18/182 • Number of events 26 • Baseline up to 96 weeks. The safety analysis set included all participants that took at least one dose of study drug.
Musculoskeletal and connective tissue disorders Musculoskeletal pain	7.1% 13/184 • Number of events 13 • Baseline up to 96 weeks. The safety analysis set included all participants that took at least one dose of study drug.	6.6% 12/182 • Number of events 12 • Baseline up to 96 weeks. The safety analysis set included all participants that took at least one dose of study drug.
Nervous system disorders Dizziness	6.5% 12/184 • Number of events 14 • Baseline up to 96 weeks. The safety analysis set included all participants that took at least one dose of study drug.	3.3% 6/182 • Number of events 6 • Baseline up to 96 weeks. The safety analysis set included all participants that took at least one dose of study drug.
Nervous system disorders Headache	12.5% 23/184 • Number of events 32 • Baseline up to 96 weeks. The safety analysis set included all participants that took at least one dose of study drug.	14.8% 27/182 • Number of events 33 • Baseline up to 96 weeks. The safety analysis set included all participants that took at least one dose of study drug.
Psychiatric disorders Anxiety	5.4% 10/184 • Number of events 11 • Baseline up to 96 weeks. The safety analysis set included all participants that took at least one dose of study drug.	2.7% 5/182 • Number of events 5 • Baseline up to 96 weeks. The safety analysis set included all participants that took at least one dose of study drug.
Psychiatric disorders Depression	4.9% 9/184 • Number of events 9 • Baseline up to 96 weeks. The safety analysis set included all participants that took at least one dose of study drug.	8.8% 16/182 • Number of events 18 • Baseline up to 96 weeks. The safety analysis set included all participants that took at least one dose of study drug.
Respiratory, thoracic and mediastinal disorders Cough	7.1% 13/184 • Number of events 14 • Baseline up to 96 weeks. The safety analysis set included all participants that took at least one dose of study drug.	6.6% 12/182 • Number of events 13 • Baseline up to 96 weeks. The safety analysis set included all participants that took at least one dose of study drug.
Respiratory, thoracic and mediastinal disorders Dyspnoea	11.4% 21/184 • Number of events 26 • Baseline up to 96 weeks. The safety analysis set included all participants that took at least one dose of study drug.	4.4% 8/182 • Number of events 9 • Baseline up to 96 weeks. The safety analysis set included all participants that took at least one dose of study drug.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	3.3% 6/184 • Number of events 7 • Baseline up to 96 weeks. The safety analysis set included all participants that took at least one dose of study drug.	6.0% 11/182 • Number of events 12 • Baseline up to 96 weeks. The safety analysis set included all participants that took at least one dose of study drug.
Skin and subcutaneous tissue disorders Hyperhidrosis	6.0% 11/184 • Number of events 15 • Baseline up to 96 weeks. The safety analysis set included all participants that took at least one dose of study drug.	3.8% 7/182 • Number of events 7 • Baseline up to 96 weeks. The safety analysis set included all participants that took at least one dose of study drug.
Vascular disorders Flushing	7.6% 14/184 • Number of events 19 • Baseline up to 96 weeks. The safety analysis set included all participants that took at least one dose of study drug.	1.1% 2/182 • Number of events 2 • Baseline up to 96 weeks. The safety analysis set included all participants that took at least one dose of study drug.
Vascular disorders Hot flush	8.7% 16/184 • Number of events 27 • Baseline up to 96 weeks. The safety analysis set included all participants that took at least one dose of study drug.	4.9% 9/182 • Number of events 9 • Baseline up to 96 weeks. The safety analysis set included all participants that took at least one dose of study drug.